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KMID : 0613820180280010043
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Journal of Life Science
2018 Volume.28 No. 1 p.43 ~ p.49
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Fortified Antioxidative Potential by Chrysoeriol through the Regulation of the Nrf2/MAPK-mediated HO-1 Signaling Pathway in RAW 264.7 Cells
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Park Chung-Mu
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Abstract
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Chrysoeriol is a widespread flavone, and it is usually found in alfalfa, which has been used as a traditional medicine to treat dyspepsia, asthma, and urinary system disorders. Recently, analysis has been conducted on the anti-inflammatory activity of chrysoeriol, but information on its antioxidative capacity is limited. In this study, the antioxidative potential of chrysoeriol against oxidative damage and its molecular mechanisms were evaluated by analysis of the cell viability, reactive oxygen species (ROS) formation, and Western blots in the RAW 264.7 cell line. Chrysoeriol significantly scavenged lipopolysaccharide (LPS)-induced intracellular ROS formation in a dose-dependent manner, without any cytotoxicity. Heme oxygenase-1 (HO-1), a phase II enzyme that exerts antioxidative activity, was also potently induced by chrysoeriol treatment, which corresponded to the translocation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) into the nucleus. Moreover, mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) were analyzed due to their important role in maintaining cellular redox homeostasis against oxidative stress. As a result, chrysoeriol-induced HO-1 upregulation was mediated by extracellular signal?regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 phosphorylation. To identify the antioxidative potential exerted by HO-1, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage was applied and mitigated by chrysoeriol treatment, which was confirmed by the HO-1 selective inhibitor and inducer, respectively. Consequently, chrysoeriol strongly strengthened the HO-1-mediated antioxidative potential through the regulation of the Nrf2/MAPK signaling pathways.
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KEYWORD
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Chrysoeriol, heme oxygenase-1, mitogen activated protein kinase, nuclear factor-erythroid 2 p45-related factor 2
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